Neuroglia contribute to the extracellular environmnt in the central nervous system by uptake or release of various ions and metabolic substances. Gliosis is a reactive state in which glia undergo distinct morphological and chemical alterations which could influence these extracellular relationships. Certain putative neurotransmitters are probably inactivated by removal from the synaptic and extracellular spaces by concentrative uptake mechanisms. Glial cells could contribute to this process of uptake inactiviation, but it is not known whether they possess the appropriate transport mechanisms. If this possible influence on transmitter action is significant, glial alterations such as gliosis could result in abnormal extracellular concentrations of neurally active substances. The first objective of the proposed research is to delineate the mechanisms by which glia interact with their extracellular environment, specifically with regard to neurotransmitters. Secondly, it is to determine the significance of this interaction in maintaining the composition of the extracellular space. Finally, it is to evaluate effects of gliosis on these normal regulatory processes. The goals can be met by determining characteristics of uptake, metabolism, and release of neurotransmitters in cultured glial cells and in brain homogenates, slices and intact brain from normal and gliotic preparations. Neurotransmitter uptake systems will be selectively identified and characterized by their kinetic properties, ionic and energy requirements and substrate, pharmacologic and stereo specificity. Neurotransmitter transport properties will initially be characterized in cultured glial cells and then compared in normal and gliotic tissue. The metabolism and release of putative neurotransmitters in these preparations will be evaluated using radiolabeled precursors and determining tissue levels, specific activities and release of the transmitter substances, particularly for the amino acid transmitter candidates. The proposed research will increase our understanding of glial cell function and should also clarify the contributton of gliosis to the neural dysfunction seen in gliotic conditions including certain forms of epilepsy.